The Yale-DRC Clinical Metabolism Core provides comprehensive support for investigators conducting clinical investigations of human diseases of metabolism such as diabetes. The primary emphasis of this core is to provide analytical resources for patient-oriented studies utilizing stable isotopes to determine metabolic flux at the whole body and tissue specific levels. Secondarily, the core also makes its analytical resources available to researchers utilizing rat and cell models of human metabolic diseases. Stable isotopes offer unique advantages over traditional radioisotopic methods for assessing substrate turnover in humans as they do not expose subjects to ioniziing radiation and they provide positional isotopomer information that can be used to assess flux through critical metabolic pathways. The major limitation to the use of stable isotopes by the clinical investigator is the need for sophisticated and expensive instrumentation and highly skilled expertise for instrument operation and for data analysis and interpretation. The Yale-DRC Clinical Metabolism Core removes these obstacles by providing the personnel and resources needed for the extraction, purification, derivatization, and instrumental analysis needed to determine the concentrations and isotopic enrichments of metabolites in plasm a, urine, or tissues. This core measures the isotopic (e.g., 2H, 13C, 15N, and 18O) enrichment and concentrations of over 140 intermediary metabolites by GC-MS, LC/MS/MS, and NMR for the calculation of turnover of carbohydrates, lipids, and proteins. The primary purposes of the Yale-DRC Clinical Metabolism Core are to: 1) make GC-MS, LC- MS/MS, and NMR analyses available to Yale DRC members, 2) avoid duplication of costs associated with personnel and instrumentation, 3.) provide standardized protocols to insure consistent and accurate sample analysis, 4) assist Yale DRC researchers in the design and interpretation of experiments utilizing stable isotopes for measurement of metabolic flux, 5.) develop new methodology in response to the emerging research needs of Yale DRC members.